The overall purpose of the NIMH-CRB program is to investigate the clinical, genetic, biological and psychosocial aspects of the nature and etiology of depression and the affective disorders. This study is the fruition of several pilot projects that have been conducted from 1973 to the present time. These pilot projects have researched the feasibility, reliability, and validity of the methods employed in this grant proposal. The proposed investigation will employ clinical psychopathological and genetic-familial methods in a sample of over 1,000 patients overall in the collaborative project. The grant application proposes two major sets of studies - clinical psychopathology and genetic and family studies. The basic hypothesis common to these studies is that the affective disorders are heterogeneous as regards etiology, clinical features, and response to treatment. Precisely defined homogenous nosologic classes validated by multiple external correlates will facilitate identification of risk factors for epidemiological studies, and verification of hypotheses as to etiology and pathogenesis.